The immune system comprises of a plethora of cell types that form an efficient network to detect invading pathogens as well as tumor cells. To carry out their function, immune cells have developed mechanisms to communicate among each other as well as with other cells within tissues, or even the pathogen. Each cell can sense various extracellular signals that are turned into intracellular biochemical changes allowing the activation of immune defense mechanisms.

Signal transduction mechanisms in leukocytes

Our goal is to understand the signaling processes involved in immune cell activation. We are focusing on the molecular and cellular mechanisms that transduce the signals received from cell surface receptors to the cellular machinery that is required to mount an immune defense.

An important factor regulating immune cell activation is the protein coronin 1, which is crucial for the activation of cell surface-triggered signal transduction and thereby regulates lymphocyte homeostasis. We are also studying how microbial pathogens evade immune recognition by hijacking host signaling networks. For example, Mycobacterium tuberculosis, which is responsible for the death of more individuals than any other bacterial infectious agent, survives within immune cells by co-opting host signaling pathways, including coronin 1-mediated activation of intracellular signal transduction.

Recent work from the laboratory suggests that this activation mechanism is operational not only in immune cells, but also in neurons. In fact, it appears that this mechanism is highly conserved among eukaryotes, with analogous signal transduction pathways being activated in amoeba, mice and human.

Signaling, immunity and host responses

While activation of the immune system should eradicate invaded pathogens, it comprises the danger to become active against non-pathogenic, so-called ‘self’ components. Such activation may lead to autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and psoriasis. Besides aiming to understand immune activation against pathogens, we are also investigating the molecular and cellular events involved in the generation of autoimmune responses.